The focus of this proposal is on the structure and function of the visual pigment rhodopsin. There are three Specific Aims: 1. To use disulfide cross-linking of rhodopsin to map tertiary contacts in the protein in both the active and inactive states. These studies will foster a better understanding of the structure of the protein and how the structure changes after exposure to light. As part of Specific Aim I the biosynthesis of split rhodopsin mutants will be explored in transfected COS cells. The formation of rhodopsin dimers and in vitro re-folding of the denatured protein will also be investigated. 2. To use a recently developed assay for transphosphorylation of rhodopsin to determine if phosphorylation of dark rhodopsin by rhodopsin kinase is a viable mechanism for the phenomenon of high-gain phosphorylation. 3. To develop a high-affinity, highly specific inhibitor of constitutively active mutants of rhodopsin found in patients with autosomal dominant retinitis pigmentosa.